Galactosemia pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dayana Davidis, M.D. [2]
Overview
Pathophysiology
- Galactose is an important metabolite of the human body both for neonatal and adult health, playing a vital role in systemic and cognitive development. [1]
Physiology
Galactose is metabolised in the body through the Leloir pathway. [2]
- It begins with conversion of B-D-galactose] to A-D-galactose
- A-D-galactose is then converted to galactose-1-phosphate by the enzyme galactokinase with utilisation of 1 molecule of ATP
- Galactose-1-phosphate combines with UDP-glucose to form UDP-galactose and the metabolically more useful glucose-1-phosphate with the help of the enzyme galactose-1-phosphate uridyl transferase.
- UDP-Galactose can undergo isomerisation in a reversible manner into UDP-glucose.
Pathology
Abnormalities in any of the enzymes involved in each of the steps of the Leloir pathway can give rise to the pathological condition called galactosemia.
- Deficiency or reduced activity of galactose-1-phosphate uridyl transferase enzyme leads to accumulation of galactose-1-phosphate [3] which:
- Sequesters phosphate essential for energy production in the human body [4]
- Inhibits enzymes involved in glucose metabolism, such as pyrophosphorylase [5]
- Inhibits galactosyl trasnferase thereby leading to defects in glycosylation [6]
- Galactokinase deficiency results in accumulation of galactose which gets converted to galactitol by a minor pathway.[7] This molecule predisposes to cataract by causing:
References
- ↑ Coelho AI, Berry GT, Rubio-Gozalbo ME (2015). "Galactose metabolism and health". Curr Opin Clin Nutr Metab Care. 18 (4): 422–7. doi:10.1097/MCO.0000000000000189. PMID 26001656.
- ↑ Holden HM, Rayment I, Thoden JB (2003). "Structure and function of enzymes of the Leloir pathway for galactose metabolism". J Biol Chem. 278 (45): 43885–8. doi:10.1074/jbc.R300025200. PMID 12923184.
- ↑ Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID http://dx.doi.org/10.1590/2326-4594-jiems-2021-002 Check
|pmid=value (help). - ↑ Gitzelmann R (1995). "Galactose-1-phosphate in the pathophysiology of galactosemia". Eur J Pediatr. 154 (7 Suppl 2): S45–9. doi:10.1007/BF02143803. PMID 7671964.
- ↑ Lai K, Langley SD, Khwaja FW, Schmitt EW, Elsas LJ (2003). "GALT deficiency causes UDP-hexose deficit in human galactosemic cells". Glycobiology. 13 (4): 285–94. doi:10.1093/glycob/cwg033. PMID 12626383.
- ↑ Coss KP, Treacy EP, Cotter EJ, Knerr I, Murray DW, Shin YS; et al. (2014). "Systemic gene dysregulation in classical Galactosaemia: Is there a central mechanism?". Mol Genet Metab. 113 (3): 177–87. doi:10.1016/j.ymgme.2014.08.004. PMID 25174965.
- ↑ Fekete E, Karaffa L, Sándor E, Bányai I, Seiboth B, Gyémánt G; et al. (2004). "The alternative D-galactose degrading pathway of Aspergillus nidulans proceeds via L-sorbose". Arch Microbiol. 181 (1): 35–44. doi:10.1007/s00203-003-0622-8. PMID 14624333.
- ↑ "StatPearls". 2022. PMID 32809518 Check
|pmid=value (help).